Transplant-Agents: A Multi-Agent Artificial Intelligence Framework for Reproducibility Assessment of Post-Transplant Risk Prediction and Rejection Biomarkers.

Reproducible biomarker identification and transplant rejection risk prediction remain fundamental yet unsolved challenges in transplantation medicine. Traditional approaches rely on hypothesis-driven analyses and domain expertise, limiting scalability and generalizability across diverse populations. We introduce Transplant-Agents, a data-driven multi-agent AI framework integrating large language models (LLMs) with machine learning algorithms for automated biomarker identification and rejection risk prediction. Agents interact through structured, iterative dialogue governed by predefined rules and criteria, converging on optimal biomarker sets reproducible across multiple iterations. We evaluated three multicenter clinical trial transplant datasets from ImmPort, comprising 683 patients across kidney, liver, and heart transplant cohorts. Transplant-Agents achieve AUROC scores of 0.93, 0.88, and 0.88. Feature importance analysis further confirms the stability, interpretability and potential generalizability of identified biomarkers. This work demonstrates that AI-agent frameworks can reliably reproduce established transplant biomarkers while enabling transparent, validated, and standardized risk prediction pipelines.